Vinay Dhingra

Intensive versus conventional glucose control in critically ill patients

BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear. METHODS Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)

Severity of illness and risk of death associated with pulmonary artery catheter use

ObjectiveTo examine the association between the use of the pulmonary artery catheter and mortality rate in critically ill patients with a higher vs. a lower severity of illness. DesignObservational cohort study. SettingA tertiary care university teaching hospital from March 1988 to March 1998. PatientsA total of 7,310 critically ill adult patients. InterventionsNone. Measurements and Main ResultsThe main outcome measure was hospital mortality rate, controlled by multivariable logistic regression within four patient groups based on severity of illness. Cutoffs for severity of illness were chosen based on Acute Physiology and Chronic Health Evaluation (APACHE) II score 25th percentiles. Logistic regression analysis demonstrated no increased risk of death associated with exposure to the pulmonary artery catheter in the population as a whole. The associated odds ratio of hospital death for the entire cohort was 1.05 (95% confidence interval, 0.92–1.21). Subgroup analysis of severity of illness revealed the highest risk of death to be associated with the lowest APACHE II score quartile vs. a decreased associated mortality rate with the highest APACHE II score quartile after adjustment with multivariable logistic regression (APACHE II <18: odds ratio, 2.47, 95% confidence interval, 1.27–4.81; APACHE II 18–24: odds ratio, 1.64, 95% confidence interval, 1.24–2.17; APACHE II 25–31: odds ratio, 1.00, 95% confidence interval, 0.80–1.24; APACHE II >31: odds ratio, 0.80, 95% confidence interval, 0.64–1.00). ConclusionsThe use of the pulmonary artery catheter may decrease mortality rate in the most severely ill while increasing it in a population with a lower severity of illness. These findings underscore the necessity of examining the effect of severity of illness in future randomized controlled trials.

Attenuation of lung inflammation by adrenergic agonists in murine acute lung injury.

BackgroundAcute lung injury leading to a systemic inflammatory response greatly increases mortality in critically ill patients. Cardiovascular management of these patients frequently involves &bgr;-adrenergic agonists. These agents may alter the inflammatory response. Therefore, the authors tested the hypothesis that &bgr;-adrenergic agonists alter the pulmonary inflammatory response during acute lung injury in mice. MethodsFive-week-old CD-1 mice received continuous infusions of 10 &mgr;g · kg−1 · min−1 dobutamine, 6 &mgr;g · kg−1 · min−1 dopexamine, or vehicle via intraperitoneal mini osmotic pumps, followed immediately by intratracheal instillation of approximately 2 &mgr;g/kg endotoxin (or phosphate-buffered saline control). Six hours later the mice were killed, and lung lavage was performed. Interleukin-6 and -10 concentrations in lung homogenates were measured using enzyme-linked immunosorbent assay. Interleukin-6 and macrophage inflammatory protein-2 mRNA was measured using reverse-transcription polymerase chain reaction. ResultsInterleukin-6 protein and mRNA significantly increased after intratracheal endotoxin (P < 0.001), and the fraction of neutrophils in lung lavage fluid increased in endotoxin-treated (41 ± 25%) versus control mice (2 ± 4%, P < 0.05). Treatment of endotoxic mice with dobutamine significantly decreased interleukin-6 protein (P < 0.05) and mRNA (P < 0.05) expression. Dopexamine had similar but less pronounced effects. Dobutamine decreased interleukin-10 expression, whereas dopexamine did not. In endotoxemic mice, both dobutamine and dopexamine decreased induction of macrophage inflammatory protein-2 mRNA (P < 0.05) and reduced the fraction of neutrophils in lung lavage fluid (P < 0.05). ConclusionsIn endotoxin-induced acute lung injury, &bgr;-adrenergic agonists can significantly decrease proinflammatory cytokine expression, decrease induction of chemokine mRNA, and decrease the resultant neutrophil infiltrate in the lung.

Fluid resuscitation in the management of early septic shock (FINESS): a randomized controlled feasibility trial

Background: It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarchvs normal saline in early septic shock, powered for a difference in mortality.Methods: At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension after ≥ 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL − maximum 3 L or 28 mL·kg−1) were administered within goal directed care for the first 12 hr.Results: Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/ site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 andP = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.Conclusion: The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock.RésuméContexte: Nous ne savons pas si la réanimation liquidienne avec des colloïdes ou des cristalloïdes chez les patients présentant un sepsis grave ou un choc septique est associée à un devenir clinique meilleur. Cette étude randomisée contrôlée a déterminé la faisabilité d’une étude d’envergure testant la réanimation avec le pentastarch par rapport au sérum physiologique en début de choc septique, avec pour objectif primaire de détecter une différence dans les taux de mortalité.Methode: Quarante patients en début de choc septique, défini comme au moins deux critères du syndrome de réaction inflammatoire, une source d’infection et une hypotension persistante après ≥ 1 L de cristalloïde ont été recrutés dans trois centres universitaires canadiens et un centre néo-zélandais. Les mesures de faisabilite étaient: le recrutement des patients, le masquage des liquides à l’étude, et I’acceptabilité des algorithmes dirigés vers des objectifs. Des bolus de normal sal in ou de pentastarch (500 mL — maximum 3 L ou 28 mL·kg−1) ont été administrés en aveugle dans le cadre de soins guidés dirigés vers des objectifs durant les 12 premieres heures.Resultats: Sur 161 patients dépistés, 121 ont été exclus et 40 patients recrutés dans le cadre de I’étude, avec un taux de recrutement de 0,75 patient/site/mois. Seulement 57 % des médecins et 54 % des infirmières ont réussi à deviner correctement le type de liquide à I’étude (P = 0,46 etP = 0,67, respectivement). Les algorithmes ont été jugés acceptables par 97 % des médecins.Conclusion: La capacité à recruter des patients pour cette étude pilote randomisée contrôlée était moins importante qu’attendue. Le masquage des liquides était satisfaisant, et les algorithmes de réanimation ont été jugés acceptables par la majorité des médecins. Des méthodes dans le but d’améliorer le recrutement sont nécessaire pour accroître la faisabilité d’une étude multicentrique sur la réanimation liquidienne en début de choc septique.

Intracranial pressure monitors in traumatic brain injury: a systematic review.

We conducted a systematic review to examine the relationship between intracranial pressure monitors (ICP) monitors and mortality in traumatic brain injury (TBI). We systematically searched for articles that met the following criteria: (1) adults patients, (2) TBI, (3) use of an ICP monitor, (4) point estimate for mortality with ICP monitoring (5) adjustment for potential confounders. Six observational studies were identified with 11,371 patients. There was marked between-study heterogeneity that precluded a pooled analysis. Patients with ICP monitors had different clinical characteristics and received more ICP targeted therapy in the ICU. Four studies found no significant relationship between ICP monitoring and survival, while the other two studies demonstrated conflicting results. Significant confounding by indication in observational studies limits the examination of isolated TBI interventions. More research should focus on interventions that affect TBI careplan systems. Further research is needed to identify which subset of severe TBI patients may benefit from ICP monitoring.

Community-acquired methicillin-resistant Staphylococcus aureus pneumonia: radiographic and computed tomography findings.

Objective The aim of our study was to review the radiologic findings of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia. Materials and Methods The hospital infection control computer database was used to identify patients who had a CA-MRSA infection with organisms isolated from blood, bronchoalveolar lavage fluid, or pleural fluid samples. Criteria for CA-MRSA pneumonia were consolidation seen on chest radiography or computed tomography (CT), growth of MRSA from sputum and/or sterile pulmonary site, clinical complaints of cough and/or shortness of breath. Chest radiographs and CT scans for 9 patients (5 men, mean age 45 y, range 35 to 71 y) were retrospectively reviewed by 2 chest radiologists. Results The most common chest radiographic finding was consolidation, which was bilateral in 7 patients and unilateral in 2 patients. The consolidation was patchy and nonsegmental in 5 and segmental in 4 patients. Two patients had cavitation evident on the chest radiograph. The most common CT scan findings were bilateral (n=8), often symmetric (n=5) consolidation, bilateral septal lines (n=7), and multiple nodules (n=5). Cavitation was present in 5 patients, either in regions of consolidation (n=5) or in large nodules (n=3). Five patients with CA-MRSA pneumonia had rapid clinical deterioration requiring ventilatory support. Two patients died. Conclusions CA-MRSA pneumonia is characterized by extensive bilateral consolidation and frequent cavitation and is commonly associated with rapid progression and clinical deterioration. CT is superior to radiography in demonstrating the presence of cavitation.

A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations

ObjectiveClinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations.MethodsMEDLINE (1966–February 2008), EMBASE (1980–February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0–100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality.ResultsTwenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62–76%)], scope/purpose [62% (95% CI 55–68%)], rigor of development [51% (95% CI 42–60%)], editorial independence [39% (95% CI 26–52%)], stakeholder involvement [32% (95% CI 26–37%)] and applicability [19% (95% CI 12–26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations.ConclusionVariation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.

Rapid Imipenem/Cilastatin Desensitization for Multidrug-Resistant Acinetobacter Pneumonia

OBJECTIVE: To report a successful case of rapid imipenem desensitization in a critically ill patient with multidrug-resistant Acinetobacter baumannii ventilator-associated pnemonia (VAP). CASE SUMMARY: A 40-year-old white man who had a lengthy stay in the intensive care unit (ICU) following a motorcycle accident developed VAP caused by A. baumannii. Treatment with imipenem was necessary due to the bacterias resistance to all other antibiotics. However, this patient was diagnosed with an allergy to imipenem following exposure earlier in his hospitalization in addition to a positive penicillin skin test. Thus, we attempted rapid desensitization to imipenem using a continuous infusion protocol. The patient was desensitized within 4 hours and was successfully treated for 21 days with a continuous infusion of imipenem combined with daily amikacin. He experienced no adverse reaction during the desensitization process or the remainder of his treatment course. DISCUSSION: The protocol used in this case was modified from a previously reported case, and differed in the speed of desensitization and total daily dose. We assumed that a more gradual escalation of the dose in our modified protocol would prevent the occurrence of adverse events, thereby resulting in more rapid desensitization. Rapid desensitization was necessary in this patient due to the presence of a life-threatening infection. The lower total daily dose of imipenem was in response to impaired renal function. CONCLUSIONS: Therapeutic options for multidrug-resistant pneumonia in the ICU are significantly limited in the presence of imipenem allergy. An option of last resort is to desensitize the patient using a rapid administration protocol. Our modified rapid imipenem desensitization protocol was successful and allowed for effective treatment of life-threatening pneumonia.

Hyperglycemia in acutely ill emergency patients--cause or effect?

OBJECTIVES To clarify the benefits, risks and timing of glucose control and intensive insulin therapy in several groups, specifically the neurologic, cardiac and septic populations of patients, commonly seen in the emergency department. METHODS Electronic search of MEDLINE (1966-2005; once with PubMed and once with Ovid) and Embase (1980-2005) using the terms insulin and glucose combined with emergency medicine, intensive care, cardiology and emergency department. RESULTS There is considerable controversy in the literature surrounding the use of strict glucose control in cardiac, neurologic and septic patients. Much of this literature is non-randomized, and the timing of therapy is poorly investigated. CONCLUSIONS Hyperglycemia is associated with adverse outcomes in acutely ill neurologic, cardiac and septic patients, but it remains unclear whether this is a causative association. Glucose control and intensive insulin therapy may be useful in some patient subgroups; however, controlled trials of aggressive glycemic control have provided insufficient evidence to justify subjecting patients to the real risks of iatrogenic hypoglycemia. We recommend a cautious approach to the control of glucose levels in acutely ill emergency department patients, with a target glucose of below 8 to 9 mmol/L.

Intensity of Continuous Renal Replacement Therapy in Acute Kidney Injury in the Intensive Care Unit: A Systematic Review and Meta-Analysis

Background and Objective: Acute kidney injury is a common finding among patients in the intensive care unit (ICU) and is an independent predictor of mortality. The optimal intensity and timing of continuous renal replacement therapy (CRRT), in critically ill patients remain unclear. The purpose of this study was to conduct a systematic review and meta-analysis of all prospective randomized controlled trials (RCTs) to determine the effect of intensity of CRRT on the survival of patients with acute renal failure (ARF) in ICU setting. Methods: Search strategy and data source. Electronic databases were searched on MEDLINE (through February 2010), ISIWeb of Science, and Cochrane Central Register of Controlled Trials (2010); Pub Med ‘‘Related articles.’’ Trial authors were also contacted for additional information. Study selection and data abstraction. All prospective clinical trials comparing the intensity of CRRT in adult patients with ARF and with explicit reporting of mortality were included. Three authors independently evaluated articles for eligibility and extracted data on study quality and outcomes. Meta-analysis used a random-effects model. Result: Of the 322 citations, 5 trials (n = 2402) were included in the meta-analysis, which met all the inclusion and exclusion criteria. Meta-analysis showed that in critically ill patients with acute kidney injury, the high-dose CRRT did not reduce mortality at 28 days. (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.70-1.11; P = 0.28). Conclusion: In critically ill patients with acute kidney injury, the high-dose CRRT did not reduce mortality at 28 days.